Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Roos, Anja; Schilder-Tol, Esther J.M.; Weening, Jan J.; Aten, Jan

doi:10.1002/jlb.64.4.503

Cited by 25 publications

(16 citation statements)

References 41 publications

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“…The TNF receptor family member CD134 is a cell surface receptor mainly involved in T cell-dependent Ab production. A strong increase in the expression of CD134 on CD4 ϩ T cells from BN rats exhibiting mercury disease has also been described (42). Recent studies have reported enhanced expression of CD134 on human CD8…”

Section: Cd45rcmentioning

confidence: 81%

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Field

Caccavelli

Bloch

et al. 2003

The Journal of Immunology

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Exposure of newborn animals to a foreign Ag may result in immunological tolerance to that specific Ag, a phenomenon called neonatal tolerance. We have previously reported that neonatal administration to Brown-Norway rats of mercury, a heavy metal toxicant, induces a dominant tolerance, specific for the chemical otherwise responsible for Th2 cell-mediated autoimmune responses in this susceptible strain of rats. Neonatal exposure to Ags can prime immunity, rather than inactivate or delete responses, and sustain regulatory functions effective against autoreactive T cells. Here, we address whether such a tolerant response is due to the generation of regulatory cells. The results suggest that the CD8+ T cell subset is involved in neonatal tolerance to mercuric salt-induced Th2 autoimmune disease. Thus, we demonstrate that in vivo CD8 depletion breaks tolerance following mercury recall in animals under a neonatal tolerance protocol. Furthermore, adoptive cotransfer of splenocytes from naive and tolerant rats as well as transfer of CD8+ T cells from tolerant animals prevent naive syngeneic rats from developing pathologic Th2 immune responses. These observations indicate that CD8+ T cells are endowed with regulatory functions in neonatal tolerance and mediate active suppression. Moreover, neonatal tolerance induced the expansion of CD8+CD45RChigh T cells and the emergence of a high percentage of IFN-γ-synthesizing CD8+ T cells, which probably reflects the implication of regulatory Tc1 cells. Thus, in vivo induction of neonatal tolerance suppresses Th2 autoimmune responses via generation of a CD8+ cell-mediated regulatory response.

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Section: Cd45rcmentioning

confidence: 81%

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Field

Caccavelli

Bloch

et al. 2003

The Journal of Immunology

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“…1 and 6). Previous studies have shown that CD40L and OX40 are induced rapidly within 24 h of antigenic stimulation (42)(43)(44)(45) and that their expression is regulated primarily by signals through TCR (42,43). Therefore, CD40L and OX40 as well as CD69 and CD25 could be early activation markers that are induced with the least concentration of Ag.…”

Section: Discussionmentioning

confidence: 98%

Naive CD4+ T Cells Exhibit Distinct Expression Patterns of Cytokines and Cell Surface Molecules on Their Primary Responses to Varying Doses of Antigen

Ise

Totsuka

Sogawa

et al. 2002

The Journal of Immunology

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The amount of an Ag used for stimulation affects the type and magnitude of T cell responses. In this study we have investigated the primary response of naive CD4+ T cells derived from OVA-specific TCR-transgenic mice (OVA23-3) upon stimulation with varying doses of the antigenic peptide, OVA323–339. IL-4 expression was maximal with 50 nM Ag and decreased significantly with increasing doses. In contrast, IFN-γ expression, which was also detected at 50 nM Ag, increased with increasing doses. The expression patterns of mRNA for the Th2-specific transcription factors GATA-3 and c-Maf were parallel to that of IL-4. These expression profiles were not altered by the addition of anti-IL-4 plus anti-IL-12 mAbs, suggesting that cytokine receptor signaling is not essential. Naive CD4+ T cells stimulated with 5 nM Ag elicited IgM secretion from cocultured B cells, whereas those stimulated with 50 nM Ag or more elicited apoptosis of B cells. This may be because at lower doses of Ag (5 nM), naive CD4+ T cells express CD40 ligand and OX40, whereas at higher doses (50 nM), they express Fas ligand. Clearly, the expression of each type of molecule depends on the Ag dose, and different molecules had different expression patterns. Thus, in the primary response, naive CD4+ T cells can exhibit different functions depending on the dose of Ag.

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“…Crosslinking of OX40 by its ligand (OX40 ligand, or OX40L) provides a costimulatory signal to T cells and this is best seen in CD4 Th2 dependent responses where crosslinking of OX40 by OX40L enhance secretion of IL-4 and IL-5. Nevertheless, OX40 does contribute to Th1 responses where it enhances secretion of IL-2 and IFN-γ [105][106][107], and the induction of anti-tumor immunity by CD8 T cells.…”

Section: Ox40 (Cd137)-ox40 Ligandmentioning

confidence: 98%

T Cell Costimulatory and Inhibitory Receptors as Therapeutic Targets for Inducing Anti-Tumor Immunity

Foell¹,

Hewes²

2007

CCDT

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Central to the normal function of the immune system is its ability to distinguish between self and non-self since failure to do so could provoke the onset of autoimmune disease. To avoid this possibility, the immune system employs several processes that include, negative selection, peripheral tolerance, and limiting DC antigen priming of naïve T cells to the lymph nodes. Naïve T cells must receive two independent signals from these antigen-presenting cells (APC) that other cells cannot provide if they are to become productively activated. The first is antigen-specific and occurs when T cell antigen receptors encounter the appropriate antigen-MHC complex on the APC--Signal 1. A second, antigen-independent signal is delivered through a T cell costimulatory molecule that engages its APC-expressed ligands--Signal 2. In the absence of a costimulatory signal T cells typically enter a state of anergy. Furthermore, the extent to which T cell activation occurs can be held in check through specific inhibitory receptors expressed on T cells. Understanding the basic mechanisms of how T cell activation is regulated has led to the development of therapeutic approaches for targeting T cell costimulatory and inhibitory pathways for turning on, or preventing the turning off immune responses in subjects with cancer. In this review we will discuss several T cell costimulatory and inhibitory pathways known to influence the development of anti-tumor immunity and how experimental manipulation of these signaling pathways has led to the generation of protective, or curative anti-tumor immunity in mice and humans.

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Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Cited by 25 publications

References 41 publications

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Naive CD4+ T Cells Exhibit Distinct Expression Patterns of Cytokines and Cell Surface Molecules on Their Primary Responses to Varying Doses of Antigen

T Cell Costimulatory and Inhibitory Receptors as Therapeutic Targets for Inducing Anti-Tumor Immunity

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